Psoriasis and Risk of Coronary Artery Disease: Detection of Early Atherosclerosis

1
Psoriasis and Risk of Coronary Artery Disease
Detection of Early Atherosclerosis

• Eric H. Yang, MD, FACC
• Assistant Professor of Medicine
• Director of the Coronary Care Unit
• Interventional Cardiology
• University of North Carolina at Chapel Hill

2
Case

• 35 year old white male with psoriasis.
• PASI score 52
• Being evaluated for systemic therapy.

• Is it true that psoriasis increases this
  patients risk of having a coronary event?
• If so, does treating the disease decrease the
  risk of future cardiac events?

3
The good physician treats the disease the great
physician treats the patient who has the
disease.
William Osler
Why? Why do you care what happens outside of
America?
July 2, 2008
George Bush
4
Outline

• Background
• Invasive Detection of CAD
• Non-Invasive Detection of Early CAD
• Surrogate Biomarkers
• Endothelial Function

5
Great Advances in Cardiovascular Medicine

• Pharmacology
• Beta Blockers, ACEI, Statins, Thrombolytics
• Coronary Interventions
• Angioplasty, Stents, Distal Protection Devices
• Prevention
• Smoking Cessation, Cardiac Rehab

6
Leading Causes of Death for All Males and Females
United States 2002
Cardiovascular Disease
Deaths in Thousands
A Total CVD (Preliminary) B Cancer C
Accidents
D Chronic Lower Respiratory Diseases E Diabetes
Mellitus F Alzheimers Disease
Source CDC/NCHS
7
Epidemiology

• 1.7 Million Americans per year suffer from a AMI,
  290,000 of which are STEMI.
• It is estimated that the number of years of life
  lost due to an AMI is 14.2 years.
• The direct and indirect cost of myocardial
  infarction to the American Society is billions of
  dollars per year.
• 12 of those who make it to a hospital will die
  from their STEMI.

AHA Statistical Update 2006
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Whatcha Talkin Bout Willis?

• Psoriasis and CAD Epidemiological Data

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General Practice Research Database (GPRD)

• 8 Million UK residents with 35 million years of
  follow up.
• Gelfand Study Divided population into 3 Groups
• Mild Psoriasis Not on Systemic Therapy (N
  127,139)
• Severe Psoriasis On systemic Therapy (N3837)
• Matched Controls N 556,955

JAMA 2006141735
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Mild PsoriasisMultivariate Cox Proportional
Hazard of MI
JAMA 2006141735
11
Severe PsoriasisMultivariate Cox Proportional
Hazard of MI
JAMA 2006141735
12
Adjusted Relative Risk of MIBased on Patient Age
Inverted Risk For Age
JAMA 2006141735
13
Swedish Inpatient Registry

• National Database of all Inpatient
  Admissions/Discharges in Sweden since 1947.
• Mallbris et. al. selected 8991 patients
  hospitalized for psoriasis.
• Compared Cardiovascular Mortality to general
  population

Eur. J Epi 200419225-230
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Inverted Risk for Age
Age
Odds Ratio
Eur. J Epi 200419225-230
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Summary

• Psoriasis appears to be an independent risk
  factor for CAD.
• The risk is greatest in those with severe
  psoriasis.
• There is an Inverted Risk for Age, that is,
  psoriasis is a greater risk factor for CAD in the
  younger population.

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Ok. We Have a Problem, But What Do We Do About
it?
ECONOMY

• Therapy and Prevention

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Associated Conventional Risk Factors
Patients
JAMA 2006141735
18
Conventional Risks

• Blood Pressure Control
• Smoking Cessation
• Aggressive Lipid Therapy
• Glucose Control

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Disease Specific Therapy

• Does disease specific therapy for psoriasis
  reduce the risk for future cardiac events?
• No current large scale trials investigating this
  question.
• In order to study effect of disease specific
  therapy on cardiac risk, we need a method for
  detecting early CAD.

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Ideal Test

• Low risk and cost to patient
• Easy to perform in serial fashion
• Reliable predictor of future cardiac events.

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Invasive Assessment of CAD
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Coronary Angiography

• Gold Standard
• Limited ability to detect early phases of
  atherosclerosis.
• Invasive

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Intravascular Ultrasound

• Small ultrasound probe that is placed
  intracoronary via a guiding catheter and wire.
• Allows look inside vessel.
• Able to detect and quantify amount of early
  atherosclerotic disease.
• Modality used in statin trials investigating
  plaque regression with therapy.
• Requires advance skill set to perform.
• More Invasive than coronary angiography.

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Summary

• Coronary angiography is of limited technical and
  practical use in detecting early atherosclerosis.
• IVUS can both detect and quantify amount of CAD
  in the early stages of atherosclerosis. Its use
  for routine clinical early detection is limited
  by its invasive nature.

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Non-Invasive Imaging
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CT Angiography

• Uses CT technology to perform coronary
  angiogram non-invasively.
• Sensitivity ok for large vessels with
  significant stenosis.
• Poor resolution in small vessels and unable to
  detect early disease.
• Significant radiation and contrast dye exposure
  limits use for serial studies.

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Coronary Calcium

• Based on theory that coronary atherosclerosis is
  associated with calcification of vessels.
• Detection method requires less radiation than CT
  angio.
• No contrast dye needed

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Risk Adjusted Hazard Ratios for Coronary Event
based on Age and Coronary Calcium Score
Raggi JACC 20085217-23
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Summary

• CT angiography is of limited use in detecting
  early disease due its limited spatial resolution.
• Coronary Calcium scoring may be practical for
  early detection.

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Biomarkers

• Can we predict events by charting levels of
  stuff?

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CRP

• Coronary atherosclerosis is believed to be a
  chronic inflammatory disease.
• The role of CRP in the mechanism of CAD is
  unknown.
• It may be directly involved in the mechanism or a
  bystander.

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CRP and CAD
Ridker NEJM 20023471557-65
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CRP in a Population Based Study
Danesh NEJM 2004350
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Lipoprotein-Associated Phospholipase A2

• Lp-PLA2 .NOT Lp(a)
• Member of the phospholipase A2 family of enzymes.
• Produced by macrophages, T lymphocytes, and mast
  cells.
• Hydrolyzes the sn2 ester bond in phospholipids
  whose fatty acid moiety has been shortened or
  altered by oxidation to yield oxidized fatty acid
  and lysophosphatidylcholine.
• These metabolites have proinflammatory
  properties16, and lysophosphatidylcholine has
  been shown to have adverse effects on endothelial
  function.

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Lp-PLA2 Adverse Cardiac Events
Brilakis EurHeartJ 200526137-144
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Long Term Longitudinal Population Based Study
Daniels JACC 2008
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Lp-PLA2 Coronary Endothelial Dysfunction ( N172)
Yang ATVB 200626106-11
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Summary

• Many biomarkers exists.
• CRP has been shown to be predictive of future
  events. It is however affected by numerous other
  factors.
• LP-PLA2 has been shown to be predictive of future
  cardiac events. It may also be directly involved
  in causing endothelial dysfunction.

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Endothelial Dysfunction

• Is this the cause of everything that is wrong
  with me?

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Coronary Endothelium

• Function
• Regulation and prevention of thrombosis.
• Regulation of vasomotor tone and coronary blood
  flow.

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Clinical Consequences of Endothelial Dysfunction

• Coronary Endothelial Dysfunction is clearly
  associated with adverse cardiac events.
• May be considered a marker for early CAD

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Endothelial DysfunctionIn Patients with Psoriasis
P Flow Mediated Dilation ()
Arthritis Care Research 200757287
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Assessment of Endothelial Function

• Invasive
• Brachial Flow Mediated Dilation
• Peripheral Artery Tone

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Endothelial Function Protocol
Diagnostic angiography
Adenosine IC 24-36 µg
Ach 10-6
Ach 10-5
Ach 10-4
NTG
Hemodynamic data Doppler velocity Diagnostic
angiogram
Infusion catheter Doppler wire
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Brachial Flow Mediated Dilation

• Measure Brachial Flow at rest and after
  occlusion.
• Correlates with future cardiac events.
• Non-invasive
• Technically demanding

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Peripheral Artery Tone

• Non-Invasive
• Less Technically Demanding than Brachial flow.
• Correlates with invasive coronary endothelial
  functional assessment.

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Summary

• Endothelial dysfunction occurs during the early
  stages of CAD.
• Assessment of endothelial function can be used as
  a method to detect early disease progression and
  regression.
• Invasive and Non-invasive methods exist.

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Conclusion

• Severe psoriasis is associated with an increased
  risk of CAD.
• The risk is highest in younger patients.
• Future studies are needed to determine if
  systemic therapy reduces this risk.
• These studies should included biomarkers and
  assessment of endothelial function.

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The good physician treats the disease the great
physician treats the patient who has the
disease.